Project Summary/Abstract Long-term Objectives: To prevent or mitigate the complications of the hemolytic uremic syndrome in children with Shiga Toxin-producing Escherichia coli (STEC) infections. Health-Relatedness of the Project: This study?s goals align with the NIAID?s mission to conduct and support applied research to better treat and prevent infectious diseases. The focus aligns with NIAID?s enteric diseases interest that includes STEC infection. The latter are a priority because of their frequency (265,000 STEC infections annually in the US) and severity as over 35% of these infections are caused by E. coli O157:H7 and 15% of infected children develop the HUS. Specific Aims Despite the conduct of numerous elegant molecular, cellular, and genomic research studies, no safe and effective interventions that reduce the likelihood of severe renal injury after STEC infections have been developed. Recent cohort studies, including several led by our group, suggest that aggressive intravenous volume expansion early in STEC infections could be nephroprotective. However, most North American clinicians continue to rely on reactive care in cases of STEC infection, namely, treating renal and hematologic consequences of STEC injury if and when they occur. Our goal is to conduct a multicenter randomized clinical trial (RCT) to assess the efficacy of intravascular volume expansion in STEC-infected children. In preparation for such trial, the following specific aims are proposed: 1) Finalize the protocol, statistical analysis plan and standard operating procedures to conduct a rigorous, safe, reproducible and generalizable multinational RCT of intravascular fluid expansion in STEC infected children; and 2) To pre- emptively address implementation, feasibility, training, recruitment, financial and ethical issues thereby ensuring the seamless, efficient, safe and successful conduct of the trial.